Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 17, Pages 7710-7715Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0910723107
Keywords
Alzheimer; Parkinson; catechine; misfolding; oligomer
Categories
Funding
- Nationales Genomforschungsnetz Plus [01GS08170, 01GS08132]
- Helmholtz Association [Helmholtz Alliance for Mental Health in an Aging Society]
- Deutsche Forschungsgemeinschaft [WA 1151/5-4, SFB 740, SFB 618]
Ask authors/readers for more resources
Protein misfolding and formation of beta-sheet-rich amyloid fibrils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimer's and Parkinson's disease. Recently, we demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis. It associates with natively unfolded polypeptides and promotes the self-assembly of unstructured oligomers of a new type. Whether EGCG disassembles preformed amyloid fibrils, however, remained unclear. Here, we show that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies revealed that the compound directly binds to beta-sheet-rich aggregates and mediates the conformational change without their disassembly into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available